Anticancer Chemotherapy and it's Anaesthetic Implications (Current Concepts).

SUMMARY
Many a times, cancer patients undergo chemotherapy before being subjected for surgery. Such patients pose some serious interactions and complications during the anaesthetic management. So, it is very important to know such interactions, and problems in advance for a smoother and uncomplicated management of anaesthesia. Herewith, a detailed review of this problem is discussed along with the current concepts and solutions.


Introduction
Cancer is treatable if detected early. Cancer is the second leading cause of death in United States 1 . It is a complex matter having special considerations. Hence,cancer patientsdeserve specialanaesthetic considerations. It requires a very closecooperation among surgeon, anaesthesiologist, and referringphysician to assure the conduct of surgicalprocedures on the patient with cancer with maximal safety.
Chemotherapy forms animportant aspect of cancer treatment. With an increased number of patients surviving for a longer period of time, a number of patients, who have received chemotherapy, may be subjected to elective and emergency surgery, therefore it is essential to know the effects of the chemotherapeutic agentson normalorgan systems. The toxicityof cancer chemotherapy drugs and their relevance to perioperative anaesthesia management relates to the specific agentsused, theircumulative dosage, and drug toxicity etc.The mostcommon toxicitiesto chemotherapeutic agents include cardiac, pulmonary, hematologic, b on e marrow, and gastrointestinal effects. Coagulopathies, thrombocytopenia, and anaemia with ulceration and bleedingofthe gastrointestinaltract may often occur. 2 .   Table 1summarizes variouscancer chemotherapy agents, their toxicities, and their relevance to the anaesthesiologist 3 . Of particular importance to the anaesthesiologist in the peri-operative period are the effects of chemotherapeutic agents on the cardio-pulmonary system as wellas theother organsystems which is discussed underneath in details.

Table 1 Common complications associated with cancer chemotherapy agents
The effects and problems occurring because of anticancer chemotherapy and it's implications on the anaesthetic management can be discussed under the following headings-A)Cardiovasculareffects andcomplications following chemotherapy B) Pulmonary effectsand complicationsfollowing chemotherapy C)Other systems affected by chemotherapy (Hepatorenal, CNS, Haemopoetic system)

A) Cardiovascular effects and complications following chemotherapy
Cancer patients receive a series of chemotherapeutic agents that may adversely affect the heart. [4][5][6] Anthracyclines; i.e. doxorubicin (adriamycin), daunorubicin,and epirubicinare thecommonest agents implicated in the development of cardiac toxicity after cancer chemotherapy. Cardiac toxicity can manifest at various times during and followingthe course of chemotherapy, three typesdepending on their appearance in relation to timing of therapy, have been identified.
Anthracycline agents may impairmyocardial contractility. 7 . Similarly, patients receivingmitoxantrone at a total dose of more than 140 mg/m 2 can suffer congestive heart failure and anthracycline-induced cardiomyopathy.Another agentknown tocause myocardial tissueinjury iscyclophosphamide 8 A cyclophosphamidedose rangeof more than 120 mg.kg -1 over2 days can result in severecongestive heart failure and haemorrhagic myocarditis, pericarditis, and necrosis. Patients receivingbusulfan inconventionaloral daily dosagemay sufferendocardialfibrosis, with signs and symptoms of constrictive cardiomyopathy. 9,10 Patients with preexisting cardiac disease receiving interferon in conventionaldoses may have exacerbations of their underlyingillness. More recently, the use ofmitomycin forextended periodsof time and dos-ages has been shown to produce myocardial damage. 11 Previous treatment with anthracyclines may enhance the myocardialdepressive effect of anaesthetics even in patients with normal restingcardiac function. 12 The preoperativeand anaesthetic assessment of the patients who have received these above mentioned agents may require 2D-echocardiogram or nuclear medicine studies. Such studies permit precise measurement of the left ventricular ejection fraction and detection of regional and global myocardial dysfunction. Where congestive failure is discovered, the physicianwill have to treat it preoperatively.
In addition to theabove sideeffects, anthracycline agents can cause dysrhythmiasunrelated to the cumulative dose. 13. Such dysrhythmias may occur hours or even days after administration. Commonly observed dysrhythmias include supraventricular tachycardia, complete heart blocks, and ventricular tachycardia. In addition, doxorubicin may prolong the QT interva1. 14 In recent years, it has been observed that paclitaxel,when given in combinationwith cisplatinum, may also produce ventricular tachycardia I5

Acute and Subacute cardiotoxicity:
It can occur immediately after a single dose or a course of anthracycline therapy. Acute toxicity commonly (40%) takes the form of ECG changes such as nonspecificST-T changes,decreased QRS voltage, and QT prolongation. Decreased R wave amplitude has beenthought by some tosignaldevelopmentof chronic cardiomyopathy later, though it is not proved. Sinus tachycardia is the most common rhythm disturbance but a variety of arrhythmias, includingventricular, supraventricular, and junctional tachycardia, have been reported. Atrioventricular and bundle-branch block have also been seen 16 .
These changes occur at alldose intervals and except for decreased QRS voltage, resolve 1 to 2 months after cessation of the therapy. Sudden death may also occur, due to ventricular fibrillation. Rare cases of sub-acute cardiotoxicity resultingin acute failure of the left ventricle, pericarditis or a fatal pericarditis-myocarditis syndrome,particularly in children, havebeen reported 17 If these patientsrecover they should not receive further treatment with anthracyclines. In elderly patients with preexisting heart disease, congestive heart failure can occur,which isgenerally transient and responds to normalmedicalmanagement.

Chronic or late cardiotoxicity:
Chronic cardiotoxicity after anthracyclines classically takesthe form of cardiomyopathy.CXR review may reveal cardiomegaly. ECG changes occur with these agents and include non-specific ST-and T-wave changes, prematureatrial and ventricular contractions, sinus tachycardia and low-voltage QRS complexes. 18 Anthracycline cardiotoxicity is a cumulative dose related phenomenon. The incidence of congestive heart failu re secon dary to anthracycline induced cardiotoxicity increases with dose. Praga et al 19 reported that an average incidence of 7% at 550 mg/m 2 , 15% at 600 mg/m 2 , and 35% at 700 mg/m 2 . At total doses 20 less than 400 mg/m 2 the incidence of CHF is 0.14%. The rapid increase in incidence of CHF after a dose of 550 mg/m 2 has made it a popular empiric-limiting dose for doxorubicin-induced cardiotoxicity.

Late onset cardiotoxicity:
Severalrecent studies, extensively reviewed elsewhere 21 have reported occult ventricular dysfunction, heart failure and arrhythmias occurringin previously asymptomatic patients more than a year after anthracycline therapy. 22,23 . It is postulated that doxorubicin can cause subclinicalmyocardialinjuryduringpreadolescent years and this in later years retards appropriate growth of the myocardium duringgrowth spurt.

Pathogenesis of anthracycline cardiotoxicity:
The anthracycline antibiotics react with cytochrome P-450 reductase in the presence of reduced nicotinamide adenine dinucleotide phosphate to form semiquinone radical intermediates, which in turn can react with oxygen to form superoxide anion radicals. These can generate both hydrogen peroxide and hydroxylradicals, whichare highlydestructive tocells thus causingmyofibrillarlysis, cytoplasmicvacuolization, and degeneration of nuclei and mitochondria in the myocytes.Severe myocytedamage resultsin decreased myocardial contractility and CHF.

Risk factors for development of anthracycline cardiotoxicity:
Apart from the total dose, patients who have received high dose radiation to the mediastinum and thosewho areon concurrentcyclophosphamide therapy areparticularly susceptibleto thiscardiomyopathy. The other risk factors are extremes of age, prior ischaemic heart disease, hypertension, valvular heart disease and liver diseases. The riskinvolved at a cumulative dose in the range of 300-450 mg/m 2 is about 1-10%, while doses higher than this invites a riskof >30%.

Investigations for the detection of anthracycline cardiotoxicity:
The bestcurrently availablenoninvasive method for assessing cardiac function is radionucleide angiocardiography. The commonly studied parameters with radionucleide studies are left ventricular ejection fraction (LVEF). A decrease in LVEF to less than 45% is considered to indicate anthracycline-induced cardiotoxicity. 2-D echocardiography is a non-invasive methodof cardiac evaluation. Diastolic dysfunction on echocardiogram mayrepresent an earlier manifestation of anthracycline toxicity. The newernoninvasive methods to know the actual myocardialdamage are by usingimagingwithmonoclonalindium -111-antimyosin antibodies. Theseantibodies bindto theexposed myosin in the necrosed myocardial cells.A diffuse uptake on imaging indicates a generalised process such as anthracyclinecardiomyopathy; afocaluptakewill suggest local pathology such as myocardial infarct. 24 Other chemotherapeuticagents also have adverse cardiac effects, which are important for the anaesthetist to know. Table 2summarizes them as follows:-

Problems with anaesthesia management:-
An appropriate anaesthetic plan includingthe invasive monitoring techniques hinges on thorough preoperative assessment. Invasive arterialblood pressure recordings and a pulmonary artery catheterization may be necessary if significant myocardialimpairment is present. Anthracycline treated patients under anaesthesia can develop acute intraoperative left ventricular failure refractory to  -adrenergic receptor agonists. Amrinone and sulmazole are the new class of cardiotonics with inotropic drugs usefulinsuch conditions.

B) Pulmonary effects and complications of cancer chemotherapy
Cancer patientscommonly sufferpulmonary complications. 75% to 90% of pulmonary complications are secondary to infection. The cancer patient can suffer infectiouscomplications secondaryto chemotherapy (e.g., Bleomycin), thoracic radiation, and multiple pulmonary resections. 25 Pulmonary complications are a significant problem; respiratory failure in cancer patients requiring assisted mechanical ventilation is associated with a75% mortality rate. [26][27][28] In patients with systemic cancer, the differentialdiagnosis of pulmonaryinfiltrates seen on a routine chest radiograph is extensive; there are many causes for such infiltrates. [29][30][31] Administration of several chemotherapeutic agents, suchas busulfan,cyclophosphamide, paclitaxel, etc, can lead to pulmonary complications. Bleomycin, an antitumour agent, is the foremost of these in producinglung damage.
Several patterns of pulmonarytoxicity produced by bleomycin have been described: 1. Dose dependent interstitialpneumonitis progressing to chronic fibrosis 2.An acute hypersensitivity pneumonitis with peripheraleosinophilia resemblingeosinophilic pneumonia.

Pulmonary veno-occlusive disease.
About 0-40% patients are reported 32 to develop pulmonary toxicity, 11-30% patients will have non-lethalpulmonary fibrosisand the mortality associated with bleomycin toxicity will range from 2-10%. Progressive interstitial pneumonitis and fibrosis is the most commonpattern of bleomycin lunginjury. Symptoms generally occur between 4 to 10 weeks after bleomycin therapy,however in about 20%patients with radiographicand histologicalfeatures ofbleomycin toxicitymay bepresent without any clinicalsymptoms. The risk factors for bleomycin pulmonary toxicity are old age, a cumulative dose >400-450 U, poor pulmonary reserves, radiotherapy, uraemia, higher inspired oxygen concentrations, and concomitantly administered other anticancer drugs.

Mechanisms of pulmonary toxicity:
Though thethreshold doselevelforthe development ofpulmonarydiseaseis inthe rangeof400to 450mg, fatalpulmonary fibrosishas beenreported with doses as low as 50mg.The mechanism of pulmonarytoxicity associated with the use of bleomycin, is probably due to Ultimately pulmonary fibrosis results. One proposed mechanism forbleomycintoxicity involvestheproduction ofsuperoxide and other free radicalmoieties, which then cleavenuclear DNA.The productionof thesehighly oxidizing radicalsmight beincreased bythe inspirationof fortified concentrationsofoxygen.

Clinical presentation:
The lesions seen frequently are in the lower lobes and sub pleural areas and chest X-ray shows bilateralbasaland peri-hilar infiltrates withfibrosis .The first signs and symptoms of toxicity are fever, cough, dyspnoea and bibasilar rhonchiand rales, which may progress to exertional dyspnoea with mild X-ray changes and a normalresting PaO 2 or a severe form of hypoxia at rest. The earliest detection of pulmonary fibrosismay be achieved through the serialevaluation of pulmonary function. Sequential measurement of carbon monoxide diffusion capacity (DLCO) may indicate the presence of occult pulmonary changes. Arterial hypoxemia is commonly found and spirometry reveals decreased lungvolumes compatible with restrictive lung disease.Regression oramelioration ofthe toxic pulmonary pathology may occur with immediate cessation of therapy. Steroidtherapy has been foundto be effective in some cases.

Hyperoxia & Bleomycin:
Of utmost importance to the anaesthesiologist is the debate about the amount of oxygen to be administered to a patient coming up for surgery after being given bleomycin. The debate was sparkedoff by a landmarkreport by Goldiner et al 34 They described 5 patients undergoingsurgery after receiving bleomycin, given> 39%oxygen intraoperatively, developed ARDS and died. Subsequent 13 patients, given > 25% oxygen, survived the surgery without pulmonary complications 35 This need to restrict inspired oxygen concentration was subsequently questioned byLa Mantia et al, who reported a series of 16 patients with uncomplicated perioperative period in spite of receiving high FiO 2 (>0.41) intraoperatively 36 A recent study by Donat et al 37 evaluating 77 patients undergoing97 extensiveresection procedures after receiving bleomycin seems to have solved the issue. Theyfound that,though the inspired concentration of oxygen was > 40%, and 25% patients did develop minor pulmonary complications; none of them developed ARDS or died. The authors concluded that perioperative oxygen restriction is not necessary and a meticulous perioperative fluid balance including transfusions as a significant predictor of postoperative pulmonarymorbidity. Theyalso noted that the duration of surgery and post-chemotherapy forced vital capacity are significant predictive factors of procedure related pulmonary morbidity. On the basis of available data it seems prudent to reduce the concentration of inspired oxygen to the lowest level to maintain SpO 2 > 90%. Intraoperative monitoringis the key to safe administration of oxygen to these patients. Arterial blood gas analysis should be performed by an indwelling arterial cannula or intermittent sampling. The judicious use of intraoperative PEEP to enhance oxygenation and the postoperative use of rigorous physiotherapy to treat ventilation-perfusion abnormalities may be preferable to the use of enriched oxygen concentrations. Fluid balance is another important factor in predicting pulmonary morbidityin-patients receivingbleomycin. Conservative fluid management isimportant; useof colloids is beneficialas compared to crystalloid.
Other chemotherapeutic agents also haveadverse pulmonaryeffects, which are very vital forthe anesthetist to understand.Table 3summarizes them as follows:-

C) Effects of cancer chemotherapy agents on hepato-renal, and CNS systems: i) Renal complications :-
Cisplatinum, acommonlyusedanticancerdrug hasbeen found to produce toxic effects like nephrotoxicity,myelosuppression, neuropathy in stocking and glove distribution, auditory and visual impairment. The dose-limiting factor for single agent use, however, is nephrotoxicity. 30% of patients receiving cisplatinum willdevelopnephrotoxicity, especially if the hydration is not properly controlled. It causes coagulation necrosis of proximaland distalrenal tubular epithelial cells and in the collectingducts leading to a reduction in the renalblood flow and glomerular filtration rate (GFR). Cisplatinum leads to wasting of magnesium and potassium. Asingle dose of 2mg/kg or 50-75mg/m 2 willproduce nephrotoxicity in 25-30% of patients 38 Acute renalfailurecan resultwithin 24hours of administration of a single dose of cisplatinum. The long-term effects were reported by Fjeldberg et al 39 who found a 12.5% reduction of GFR after 16 to 52months afteradministration of cisplatinum. Proper hydration with forced diuresis seems to decrease the incidence of renal toxicity by reducingthe concentration of cisplatinum in renaltubules andthe amount of time it remains in contact with renal tubules. Use ofnormalsalineis particularly beneficialas high chloride concentrations in thetubules inhibitthe hydrolysis of cisplatinum. The renaltoxicity may be accen-tuated if thepatient receives aminoglycosides concomitantly. The newer analogues of cisplatinum, such as carboplatinum and oxaloplatinum areless nephrotoxic withequalefficacy in controllingthe malignancy.
Methotrexate causes the acute nephrotoxicity as a result of its intratubular precipitation 40 .
Other chemotherapeuticagents also have adverse renal effects are summarized in the Table 4as follows:-  ii) CNS complications:-Vinca alkaloids were the first anticancer drugs found to have neurotoxic effects. Vincristine is probably the only drugwhose dose limiting toxicity is neurotoxicity. It can affect the central, peripheral or the autonomic nervous systems. Peripheral neuropathies present as peripheral paresthesias with depression of deep tendon reflexes. The paresthesias progress proximally with therapy. Motor dysfunction and gait disorders can occur. Vincristine, 41 vinblastine, procarbazine, cisplatinum 42 all can cause a toxic neuropathy with paresthesia, loss of deep tendon reflexes and muscle weakness.
As far as regionalanaesthesia is concerned, one should be aware that in a considerable percentage of patients a sub-clinical, unrecognized neuropathy may be present in patients with previous cisplatinum chemotherapy. Recently, adiffuse brachialplexopathy after interscalene blockade has been reported in a patient receiving cisplatinum chemotherapy. Thus, if regionalanaesthesia is contemplated, a detailed pre-operative neurologicalexamination andcarefulassessment of the risks and benefits is warranted. 44 Other chemotherapeuticagents also have adverse CNS effects are enumerated in the Table 5as follows:-

iii) Hepatic complications :-
Hepatocellular dysfunction is manifested as raised serum enzymes, fatty infiltration of liver and cholestasis, due to direct toxic effect of the drug or it's metabolite. L-asparginase and cytarabine are most commonly implicated agents inhepatocellular dysfunction. Adecreased synthetic function with low proteins and coagulation abnormalities may be seen. Ascites, painful hepatomegaly, and encephalopathymay result afteradministration of cytarabine, cyclophosphamide, mitomycin, etc.

D) Miscellaneous adverse effects of cancer chemotherapy agents:
i) Haematological complications:-Bone marrow function in cancer patients may be disturbed by primary bone marrow disorders (e.g., leukemia), bony metastases (e.g., from breast cancer), as well as myelosuppressive chemotherapy.The production of any or all blood elements may be impaired. There is dysfunctional coagulation. The PTand PTTare shortened. There is increase in factor I, V, VIII, IX, XI and FDP. There is reduced survival of the platelets and the decreased antithrombin III activity. There areno prospective trials to datethat establishthe minimalplatelet count necessary to prevent bleedingwith specific procedures. Some investigators have maintained a minimallevel of 50,000 platelets per microliter in the intraoperative and postoperative period.Correction of other coagulation disturbances is important before undertaking surgical intervention in the thrombocytopenic patient. In view of these findings, a close cooperation among the surgeon, anaesthesiologist, and hematologist is required for optimalmanagement and maximal safety. 45 Myelo-suppression causedby allthe chemotherapeutic agents is partiallyor completely reversible within 1 to 6 weeks of termination of therapy.

iii) Steroid administration:
The oncology patient often has a history of exogenous glucocorticoid administration as part of a chemotherapy regimen. The physician at the time of preoperative evaluation has to decide on the use and the amount of stress steroid coverage. The patient who has received >2 weeks of glucocorticoids within the past yearis considered at riskfor adrenalsuppression. However, many of these patients are capable of a normal stress response. The corticotrophin (ACTH) stimulation test is the definitive test to identify adrenal suppression.

iv) Tumor lysis syndrome:-
Another frequently seen complication in cancer patients is the tumor lysis syndrome. 47 Chemotherapy induces rapid tumor cell lysis in patients with a large malignant cellburden over an exquisitely sensitive tumor 48,49 Thisclassically occursin patientswith Burkitt's lymphoma,non-Hodgkin's lymphomas,acute lymphoblastic and nonlymphoblastic leukemias, and chronic myelogenous leukemia. In addition, it may also occur continuously in patientswith lymphomasand leukemia following treatment with chemotherapy,radiation, glucocorticoids,tamoxifen, orinterferon. The clinical manifestationsof this syndrome are related to the metabolic abnormalities.
In those patients with suspected tumor lysis syndrome or for those patients who receive chemotherapeutic agents likely toinduce thesyndrome, prevention is the mainstay of treatment. To prevent the development of acute renalfailure, patients who are to undergo treatment for malignancies should receive vigorous intravenous hydration,often with diuretics or renal doses of dopamine to ensure adequate urine output.

v) Chemotherapy and wound healing:-
The outcome of surgical procedures may be affected by the wound-healing impairment caused by antineoplastic agents used to treat the underlying tumor. The neutropenia that accompanies some chemotherapy within 7 to 10 days of administrationcan interfere with the early phases of wound healing. Most patients with WBC count 500/mm 3 have no adverse effects of leukopenia on surgical wound healing. Chronic anemia also has little effect on surgicalwound healing 50. The effects of chemotherapy directly on wound healing depend on dose and the timing of drug administration relative to creation of the wound. Ahigh incidence of wound complications has been reported in women undergoingmastectomy after receiving preoperative chemotherapy andradiation. Bleomycin has not been associated with increased wound complications.

Anaesthetic considerations for patients after chemotherapy
The interaction between ananaesthesiologist and a cancer patient starts with a preoperative visit for a surgical procedure. The goals of such a preoperative visit would be as follows:-To optimize patient's physical status. To assess effectsof cancer and cancer therapies (chemotherapy, radiotherapy, and surgery) on patient.
Some of the important features and care before planninganaesthesia in such achemotherapy received patient are as follows - In pre-anaesthetic checkup, one must obtain a pertinent, comprehensive past medicalhistory, preexisting conditionsprior to surgery andanaesthesia, medications, allergies, family history and a complete systemicexamination. Theanaesthesiologist's role in preoperative evaluation and preparation of the surgical patient and intraoperative and postoperative management is of great importance. This begins with a thorough history and physicalexamination.
 Routineclinicaltestslike complete blood count, urine analysis, serum electrolytes, fastingblood sugar, serum BUN, pulmonary function tests, PaO 2 and PaCO 2 contents by arterial blood gas analysis, serum osmolality, bilirubin, creatinine, amylase,liver function tests, chest X-ray and ECG are mandatory. 51 Awareness of the side effects of the various chemotherapeutic agents enables other appropriate investigations to be carried out and institution of corrective measures when possible will ensure a well-prepared patient.
 Immuno-suppresion occurs with the use of all the alkylatingagents. Meticulousattention mustbe given to aseptic techniques in the perioperative period in order to avoid potentially lethaliatrogenic infection.
 Pneumonitis and pulmonary fibrosis may be induced by many of the chemotherapeutic agents. History or symptoms suggestive of exertionaldyspnea or dyspnea at rest should alert the physician to this problem .In addition to chest X-ray, arterial blood gases arenecessary. Pulmonaryfunction tests including arterial blood gas, spirometry, and carbon monoxide diffusing capacity should be evaluated. Findings compatible with interstitialfibrosis include increased alveolararterialgradient, restrictive lung disease, and decreased carbon monoxidediffusing capacity. 52 Patients who had a bleomycin therapy should not receive high inspired oxygen concentrations and thatcolloid rather than crystalloid replacement should be preferred bothduring and after surgery. Ventilator support should be anticipated in the postoperative period.  Cardiotoxicity may occur in-patients who have received anthracyclines. The ECG may reveal diminution ofthe QRS voltage, systolictimed intervalmay be increased, and ejection fraction as well as fractional shorteningmay be decreased. Congestiveheart failure is treated using diuretics,digitalis and oxygen. Operating andrecovery room monitoringshouldinclude ECG, urinary output, central venous pressure and when feasible pulmonary arterial and wedge pressures. Huetteman and colleagues 12 showed thatprevious treatmentwith anthracycline might enhancethe myocardial depressant effects of anaesthetics even in individuals with healthy cardiac function at rest.  Hepatotoxicity may occur withthe useof most of the anticancer drugs.Anaestheticdrugs incriminated, as causingliver damage should not be administered. Busulfan, methotrexate, cisplatinum and others may cause nephrotoxicity. Balanced electrolyte solutions started the eveningbefore surgery will aid in maintaining optimalrenal flow and glomerular filtration. Potentially nephrotoxic drugs should be avoided.
 The effects of cyclophosphamide, a pseudocholinesterase inhibitor, could last for 3-4weeks from the end of its use, and Zsigmond and Robins 53 argued that this occurrence might justify or explain the recognised hazard because of the drug's interaction with suxamethonium (a depolarising muscle relaxant, metabolised by pseudocholinesterase), inducing a risk of protracted postoperative apnoea.  Negative interactions between methotrexate and non-steroidal anti-inflammatory drugs (NSAIDs) are well known.Although the mechanism of this interaction is not completely clear, NSAIDS are known to reduce the excretion of methotrexate.A competition for receptor sites at renaltubular excretion has been postulated but the mechanism is not yet understood; this interaction might result in potentially fatal side-effects for patients. 54  Central and autonomic nervous system toxicity and peripheralneuropathies occur with vincristine, cisplatinum and others. Thereforeregional anaesthesia is contraindicated. Thepreoperative state of sensorium and neurologic deficits should be documented. Anticholinesterase effects of alkylating agents are significant. Reduction of dosage of succinylcholine is indicated to prevent prolonged respiratory depression. Monoamine oxidase like inhibitionmay occur with the administration ofprocarbazine. Because of synergistic action barbiturates, antihistaminic, phenothiazines, narcotics and tricyclic antidepressantsshould be used with caution. Diarrhea is a side effect of many of the anticancer drugs. Attendant serum electrolyte and fluid abnormalities should be corrected before surgery and also in the postoperative period.
The cancer patient like any other high risk patients requiring anaesthesia deserves a specialcare and considerations.Agrowingnumber of patients undergo surgicalprocedures with general anaesthesia soon after receivingchemotherapy; occasionallysuch treatment can be given duringsurgery. Therefore, it is worthwhile and prudent to understandthe pathophysiology of cancer and consider the pharmacologicalinteractions between anticancer and anaesthetic drugs. Anti-cancer chemotherapeutic drugs may cause generalized and specific organ toxicities and may also give rise to various unpredictable or life-threatening peri-operative complications, rendering a detailed pre-operative assessment of patientswith previous chemotherapy mandatory. Thus,special consideration and understanding of the cancer patient's anaesthesia-related needs will result in superior patient care and outcomes.
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